Efficacy and safety of oral tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphomas: A systematic review and proportionality meta-analysis.

Abstract

e19045 Background: B-cell non-Hodgkin lymphomas (NHL) are a diverse group of malignancies with varying prognoses, and managing relapsed or refractory (R/R) cases remains challenging. Tazemetostat, an oral EZH2 inhibitor, has received FDA approval for relapsed or refractory (R/R) non-Hodgkin B-cell lymphomas in adults, including those with mutant EZH2 or limited therapeutic options. Early trials demonstrated its promising efficacy and safety, but long-term outcomes remain unclear. This meta-analysis evaluates the efficacy and safety of tazemetostat in managing R/R B-cell non-Hodgkin lymphomas. Methods: A systematic review was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov databases using MeSH terms and relevant keywords. The search, conducted up to December 20, 2024, identified studies assessing Overall Response Rate (ORR) and 1-year and 2-year Progression-Free Survival (PFS). Random-effects meta-analysis using the Mantel-Haenszel method was applied to synthesize proportional outcomes via R-studio. Results: The meta-analysis included three phase 2 trials and two phase 1 trials, encompassing a total of 241 patients with relapsed or refractory B-cell non-Hodgkin lymphomas treated with oral tazemetostat (800 mg twice daily). Using the random-effects model, the pooled analysis of five studies revealed that 55% (95% CI: 41.4–67.5%) of patients achieved a positive tumor response. Despite moderate heterogeneity (I² = 70.7%, p = 0.0085), these findings highlight the promising efficacy of tazemetostat, with over half of the patients showing significant tumor reduction. Additionally, a meta-analysis of three RCTs assessing 2-year progression-free survival (PFS) demonstrated a 2-year PFS rate of 10% (95% CI: 0.6–64.7%), with high heterogeneity (I² = 93.8%, p < 0.0001). In contrast, the 1-year PFS was 50% (95% CI: 29.4–69.9%), albeit with significant heterogeneity (I² = 83.6%, p = 0.0022). Conclusions: This systematic review and proportionality meta-analysis evaluated the efficacy and safety of tazemetostat in relapsed or refractory B-cell non-Hodgkin lymphomas. The results showed a 55% tumor response rate and 49.6% progression-free survival (PFS) at 1 year, but only 10% achieved PFS at 2 years. While tazemetostat demonstrates promising short-term efficacy, limited long-term benefits and significant study heterogeneity highlight the need for further trials with larger sample sizes.